the effect of empagliflozin on nafld in asian patients with type 2 diabetes

Conditions: Type2 Diabetes; NAFLD

Summary: non-alcoholic fatty liver disease( nafld) is common in patients with type 2 diabetes. empagliflozin, an fda-approved oral medication used to treat type 2 diabetes, has been shown to reduce production and deposition of fat in the liver in animal experiments. there is little published evidence that this is so in asian patients with type 2 diabetes. the investigators designed this pilot study to determine if use of empagliflozin for 6 months in patients with type 2 diabetes can improve scan, blood marker and biopsy features of nafld.

empagliflozin, an fda-approved sglt2 (sodium glucose transporter 2) inhibitor used to treat type 2 diabetes, has been shown to reduce hepatic de novo lipogenesis and hepatic steatosis in animal models. there is little published evidence that this is so in asian patients with type 2 diabetes. the investigators designed this open label proof of concept trial to determine if use of empagliflozin for 6 months in patients with type 2 diabetes can improve biomarkers and histological features of biopsy proven nafld. hypotheses 1. 6 months of empagliflozin will result in improved histology on liver biopsy in type 2 dm patients with nafld 2.6 months of empagliflozin will result in changes in liver enzymes, adipocytokines and fgf levels in type 2 dm patients with nafld 3.6 months of empagliflozin will result in improved liver stiffness measurement in type 2 dm patients with nafld study protocol this is a prospective open-label proof-of-concept study. the investigators plan to recruit 25 asian patients with biopsy-proven nash and type 2 diabetes and commence them on empagliflozin 25 mg daily for 6 months. upon recruitment clinical information will be obtained via an interview and use of a structured questionnaire. anthropometric measurements will be obtained at baseline and 6 months. a repeat liver biopsy will be performed after 6 months of empagliflozin therapy. mri and fibroscan of the liver will be conducted at baseline and 6 months. fasting blood samples will be drawn for glucose, insulin, c-peptide, triglyceride, hdl, ldl, total cholesterol, nefa(non-esterified fatty acid), hba1c , liver function test(including albumin, ast, alt, gamma gt, uric acid, inflammatory markers, fgf(fibroblast growth factor) and other biomarkers at baseline and 6 months. patients will be reviewed by a physician at 1 month and 6 months for development of any potential adverse events while on empagliflozin therapy. patients will be instructed not to make any significant changes to diet and lifestyle in these 6 months in order to assess to full effect of the intervention with no possible confounding factors.

Eligibility criteria:
inclusion criteria: * biopsy proven nash * type 2 dm * hba1c :\>6.5% * bmi \< 45kg/m2 * any anti-diabetic agent except sglt2 inhibitors, tzds(thiazolidinediones), dpp4(dipeptidyl peptidase4) inhibitors and glp1 ras(glucagon-like peptide 1-receptor agonists) exclusion criteria: * egfr \<45 ml/min * structural and functional urogenital abnormalities, that predispose for urogenital infections * investigational product use in the last 6 months * sglt2 inhibitor, tzd, dpp4 inhibitor and glp1 ra use within the past 6 months * dka(diabetic ketoacidosis) or hhs(hyperosmoloar hyperglycaemic syndrome) within the last 6 months * pregnancy * presence of major contraindications to magnetic resonance imaging (cardiac pacemakers, claustrophobia, foreign bodies and implanted medical devices with ferromagnetic properties). * liver cirrhosis * type 1 diabetes * severe uncorrected insulin insufficiency * significant alcohol intake * hiv infection * use of traditional chinese medication or alternative therapies * coexisting causes of chronic liver disease - chronic viral hepatitis(b \& c), autoimmune liver disease, hemochromatosis, wilson's etc. * use of medications associated with steatosis eg. methotrexate, anticonvulsants, antiretroviral therapy etc. * h/o stroke * steroid therapy * endogenous cushing's * familial hypertriglyceridemia